Water → Trifluoroacetic acid

HRID 1506522Notes

Reaction equation

HRID 1506522 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20]([CH:25]=O)=[CH:19][CH:18]=5)[C:8]=2[C:27]([F:30])([F:29])[F:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:31]([CH2:35][CH2:36][OH:37])[CH2:32][CH2:33][OH:34].C(O[BH-](OC(=O)C)OC(=O)C)(=[O:40])C.[Na+].C([BH3-])#N.[Na+].[OH2:56]>ClCCCl>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20]([CH2:25][N:31]([CH2:35][CH2:36][OH:37])[CH2:32][CH2:33][OH:34])=[CH:19][CH:18]=5)[C:8]=2[C:27]([F:29])([F:30])[F:28])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:8]([OH:40])([C:27]([F:30])([F:29])[F:28])=[O:56]

Participants

8

Reactant 5

HCID 962WaterHCID 8113DiethanolamineHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 866698753-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde

Product 2

HCID 6422Trifluoroacetic acidYield 51.6%HCID 671700962,2'-((3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylazanediyl)diethanol

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 88A, 20 mg, 0.049 mmol), diethanolamine (18.68 mL, 0.195 mmol), 1,2-dichloroethane (1 mL) and sodium triacetoxyborohydride (31.0 mg, 0.146 mmol) was stirred at room temperature under nitrogen for 2 days. Sodium cyanoborohydride (20 mg, 0.318 mmol) was then added. The mixture was stirred at room temperature for 1 hr before water (1 mL) was added. The aqueous layer was extracted with dichloromethane (2×1 mL). The combined organic solutions were concentrated under reduced pressure. Purification using reverse phase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration and lyophilization gave 2,2′-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylazanediyl)diethanol, TFA (15.6 mg, 0.025 mmol, 51.6% yield) as a white solid. The compound had an HPLC retention time=3.20 min. (condition C); LC/MS M+1=500.1; 1H NMR (400 MHz, MeOD) δ ppm 8.06 (1H, d, J=7.9 Hz), 7.77 (2H, d, J=7.5 Hz), 7.56-7.72 (5H, m), 4.55 (2H, s), 3.94 (4H, t, J=5.2 Hz), 3.39 (4H, t, J=4.8 Hz), 3.07-3.18 (4H, m).

Workup

  1. additionwas added
  2. extractionThe aqueous layer was extracted with dichloromethane (2×1 mL)
  3. concentrationThe combined organic solutions were concentrated under reduced pressure
  4. customPurification
  5. concentrationphase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration and lyophilization

Sources & evidence

ORD record
ord-a1739dcce8e64c2fa13687f4755849bb
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

Loading…